LIFETIME

In 1946, scientists started tracking thousands of British children born during one cold March week. On their 65th birthday, the study members find themselves more scientifically valuable then ever before.
BY HELEN PEARSON

Study of a

O

n Tuesday 5 March 1946, Patricia Malvern was born in a small flat in Cheltenham, UK, near the boilers that her dad stoked to warm the building above. She weighed in at 9 pounds, 2 ounces (4 kilograms). The next day, David Ward was “one of the few Catholics born in a Jewish hospital” opposite Hampton Court, near London. Ward doesn’t know exactly what he weighed, although his dad said later that he looked “like a skinned rabbit”. Throughout the rest of that week, just months after the end of the Second World War, 16,695 babies were born in England, Scotland and Wales. Health visitors carefully recorded the weights of the vast majority on a four-page questionnaire, along with countless other details including the father’s occupation, the number of rooms and occupants (including domestics) in the baby’s home and whether the baby was legitimate or illegitimate. Over subsequent years, the information files on more than 5,000 of these children thickened, then bulged. Throughout their school years and young adulthood and on into middle age, researchers weighed, measured, prodded, scanned and quizzed the group’s bodies and minds in almost every way imaginable. This week, the group has much to celebrate. They are turning 65, the age at which many in the United Kingdom retire and, as such, a milestone in British life. They will also celebrate being part of the longest-running birth-cohort study in the world. These ordinary men and women are now some of the best-studied people on the planet. And this makes them some of the most scientifically valuable, because it has allowed researchers to track their health and wealth throughout their lives, and to search for factors that could explain their trajectories. The exercise has revealed some surprises. It has shown that the heaviest babies were most at risk of breast cancer decades later; that children born into lower social classes were more likely to gain weight as adults;

that women with higher IQ reached menopause later in life; and that young children who spent more than a week in hospital were more likely to suffer behaviour and education problems later on.

All told, the results from the 1946 birth cohort — now known as the National Survey of Health and Development and run by the Medical Research Council (MRC) — have filled 8 books and some 600 papers so far. Perhaps more than anything else, the survey has shown that early life matters — a lot. “Ultimately, where you get to in early adulthood is strongly influenced by where you come from,” says Michael Wadsworth, who led the study for nearly 30 years, until 2007. Children who were born into better socioeconomic circumstances were most likely to do well in school and university, escape heart disease, stay slim, fit and mentally sharp and, so far at least, to survive. (Ward, whose father worked his way up in a Walthamstow-based drycleaning business, went on to university and built a career in journalism. Malvern, whose father left home when she was five and who wore third-hand clothes, left school at 16 and “bitterly regrets” the fact that her mother couldn’t afford to pay tuition for her to train as a teacher.) Those lessons are arguably more urgent today NATURE.COM than they were in 1946 when, caught up in postListen to a podcast war optimism, Britain was introducing major about the 1946 birth- educational reforms and a National Health Sercohort study at: vice (NHS) to ensure that good schooling and go.nature.com/7rhmk3 health were available to all. The contrast with the

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“It’s unique and groundbreaking in the history of epidemiology.000 (US$14.” says Diana Kuh. Students have been rioting to protest against the government’s plan to introduce £9. who now directs the survey and says she is saving up for her grandchildren to attend university. logistically nightmarish and financially prohibitive: sending health visitors to interview the mothers of every child born in that March week. He set about launching an investigation that today would be ethically difficult. who inherited the study leadership from Douglas more than three decades later. James Douglas was appointed to head it. who studies the impact of child poverty. memory and how quickly they could get up from a chair. running from 2006 to 2010 and costing £2. 3 M A RC H 2 0 1 1 | VO L 4 7 1 | NAT U R E | 2 1 © 2011 Macmillan Publishers Limited. He says that cohort research has been vital in seeding the idea that disease evolves as a result of events throughout life. Irvine. study members underwent almost every modern biomedical test. Some are testing how genes interact with a lifetime of experiences to lead to obesity or disease. by early birth weight or by life’s inequalities — that alter gene expression and might provide a molecular explanation for effects in later life. had spent part of the war conducting vast studies of air-raid casualties. for which the cohort’s data once helped provide impetus. DUNHAM/NATURE The first few decades of the twentieth century found Britain acutely concerned about its falling birth rate and stagnant infant mortality. The data will provide a detailed starting point from which to measure the cohort members’ inevitable decline. Greg Duncan.” says Wadsworth.” says Ezra Susser. “I find these changes very worrying. “This is what it is to be human and normal.” M. and the opportunity to analyse the information is already swelling an extensive network of collaborators. It’s the only study to have chased an entire cohort across its life course — and it’s not yet finished. a physician. and sweeping budget cuts are threatening public services — including early childhood support centres. from blood pressure right down to genes. In the latest round of data collection. “These are real people. and life as it is actually lived that makes the cohort study so unusual.600) annual fees for universities. (The thought at the time. plans are afoot to drastically reform the NHS (eviscerate it. an economist at the University of California.” Now. whole-body bone. country’s mood this winter couldn’t be starker. Douglas. muscle and fat scans.PICTURE CREDIT Diana Kuh leads the UK National Survey of Health and Development. whose populations are rapidly ageing and sickening. hopes that follow-up studies could help to answer a question arising from the earlier findings on socioeconomic status and health: “What are the active ingredients in social class?” It is this ability to draw associations between biological data. He reached 13. as Kuh puts it.” says Kuh. was “how are we going to maintain Britain and its empire?”) A Population Investigation Committee recommended a maternity survey to explore whether the social and economic costs of childbearing were discouraging prospective parents. critics say). an epidemiologist who works with cohort studies at Columbia University in New York. the study offers a precious opportunity to understand how a lifetime of experiences might hasten or slow their decline — an urgent question for countries such as the United Kingdom and United States.687 of them. measures of blood-vessel function. All rights reserved . “It was crazily ambitious. and tests of blood. including echocardiograms. as the cohort members enter old age. others plan to scan participants’ genomes for ‘epigenetic’ marks — molecular traces left. say its leaders. Yet “he pulled it off ”.000 people since their birth in 1946. perhaps.7 million. “You gain enormous depth of understanding in how that disease came to be by following someone over their life course. which has compiled thick files on more than 5.

and Douglas was heading towards retirement. even Douglas thought the project was finished. that could explain the link between birth weight and breast-cancer risk. heart and lung function. who published middle classes were more likely to pass the a 1989 analysis of birth weight and health in 11+ and do well at school than were equally a different cohort2. spurred a parliamentary bill allowing more midwives to deliver gas and air. was planning to buy a house. The MRC. Correlations tumbled out of the data. Small babies were more likely to them. Those who grew fast rassed by taking free school meals. but we find an endless stream of schools in the 1960s. for example. He wanted to see how these indicators had been influenced by earlier life — and then chart them into the future. regardless of background. He found that babies with bright working-class children. which had been funding the project since 1962. lege London (UCL). occupations and social mobility had been answered. diabetes. One widely reported result showing that only 20% of women who gave birth at home were offered pain relief. a link that became known as the Barker hypothesis after To the architects of the welfare state. including blood pressure.362.687 children spanning geography and social class. 11 and 15. looking for changes bers’ education. Malvern would sleep without covers in order almost in a poetic way. Bright children from the versity of Southampton. He was one of 4 children out ics: the chemical footprints. a child’s odds. an oncologist at University ColAs the 1970s rolled on and the participants entered their thirties. and tracked their course through school. In 1985. and in 1976 with his son and daughter. “Big babies were more likely to get diverging paths.” 11+. After he took the helm in 1979. he realized that he had the perfect weapon for testing the success of the 1944 Education Act. “It isn’t the same story introduction of non-selective ‘comprehensive’ every time. the baby boom was in full swing and concerns about birth rate had mostly dissipated. is planning to analyse tens of thousands Douglas was losing steam. cancer and educational references and contributing to the schizophrenia risk. growth and other data were regularly recorded and then transferred onto punch cards. turning Douglas’s next nections between infant and child growth or two books — The Home and the School (1964) development and adult traits from cognitive and All Our Future (1968) — into must-read ability to frailty. and who that spans all those years. determined at that stage. But the volume. ending up with 5. when they started to sicken and die. meanwhile. long-term associations in quite ‘noisy’ data. WARD . that there is something to catch a cold and avoid school. Maternity in Great Britain. “I thought the changing pattern of health of these people would be interesting over life. interesting again. says Widschwendter. although supthe lowest birth weights had the highest risk portive parents and good teachers could better of heart disease as adults. failed her postnatally have more cardiovascular risk. such as methyl groups. whose health.”) the exam. dithered about what to do with it. an epidemiologist at the Uniwere discouraging. when Douglas’s book about the study’s results appeared. UK. Martin Widschwendter. Medical epidemiologists The detailed life-course information that can be combined with the DNA thought that the cohort should be mothballed until its members got “is really only available via these cohorts”. and his mother tested are lasting scars laid down on them? One possible answer lies in epigenethim on Latin vocabulary over the ironing. made a stir by revealing shocking disparities between rich and poor in infant survival and women’s care. Ward’s systems in infants are so important. It was an early hint that fetal and infant growth shape adult health. Most of his questions about the cohort memof possible methylation sites in the cohort’s DNA. He selected a sample of the original 13. obesity. Malvern went A major question for scientists today is how David Ward as a baby in 1947 with his mother and to learn typing at Government Communicato explain these connections: which biological sister. the children were walking breast cancer.” While Douglas was studying the group’s says Kuh.” he says. diet and exercise. In particular. All rights reserved COURTESY OF D. who was cripplingly embarhave poor grip strength. which had introduced a nationwide system of exams for 11-yearolds — the 11+ — intended to channel the brightest. into elite ‘grammar’ schools. it was just getting going. then again at 43 and 53. She blames a class teacher so violent that (Says Ward: “I find that quite extraordinary. stamped on DNA by of 66 in his school’s top two classes who passed the 11+ exam. tions Headquarters in Cheltenham. and he early life events that alter gene-expression patterns and might contribute and his sister were the first in their family to attend university. For Wadsworth. Wadsworth and his team reported that cohort members whose birth weight had been low had higher blood pressure as adults1. showing a tangle of conas the ‘waste of talent’. the results David Barker. He started assessing the group’s physical capabilities and health. Malvern. and how father. to later disease.NEWS FEATURE In 1948. and that the poor suffered most. Douglas also tested the children’s cognition as they reached 8. 2 2 | NAT U R E | VO L 4 7 1 | 3 M A RC H 2 0 1 1 © 2011 Macmillan Publishers Limited. Wadsworth convinced the MRC to fund a new round of data collection as the cohort reached 36. After she left school. that something was “walloped me across the head” on the day of set down. Douglas decided to turn the study into a tool for documenting social inequality and gauging the impact of newly minted welfare reforms such as the NHS. The attrition of smart but poor Study after study from the 1946 cohort boys (girls counted for less) became known supported the link. a social epidemiologist who had joined Douglas’s team in 1968.

as the cohort neared 60 and Wadsworth neared the end of his scientific career.FEATURE NEWS for longer. She weighed paper summarizing the latest data goes pub11 ½ stone (73 kilograms) when she moved. Marcus Richards. and last November and the cheese and having visitors. Malvern has since lost cope with the increased data sharing. published a study of two tests tended to reach menopause several years hot genes called FTO and MC4R. he says. members’ homes. she found that the everything we had at that to see if we could make that association go association of those variants with body mass index increased in early away and it didn’t. staff and 100 collaborators — are still compilSomewhere on one of those curves is Maling such truths about their thousands of parvern. Kuh argued. Kuh is expecting the queue of epidemiolo“When I came back in 2000 I was horrified: I gists. Once her stopped work as a school bursar. He learned that he has signs of osteobabies. who found her own weight creeping up ticipants.” says Kuh. At least one study has hinted at the power As women in the study reached their fifties. don’t want to admit that you had that extra glass As the cohort approached their thirties. no social class was immune. and so was able to sustain reproduction Ever protective of her study members and the limited DNA samples © 2011 Macmillan Publishers Limited. where “you can’t monitoring participants’ health and trying to get anywhere without going up and down a hill”. the line of plonk or another slice of cake. as some epidemiologists expect. tease out the influence of early experience.” she thinks — she hired someone for three years especially to on top of the menopause. she prefers the more optimistic idea that disease risks Kuh — who had trained in economics — wanted to build up the bioresult from an accumulation of experiences throughout life. were porosis in his spine. “We can take that the MRC to pay for every willing cohort memresearch and say. now housed in a Georgian tershould do it. any effects of the genes on appetite or fat storage were overhood cognition provides a readout of brain development. in their late thirties it soared3. and this is how you research unit. “Now the cohort is one of the most when she moved to Luxembourg in 1992 and phenotyped in the world. Last year. As the weight. the study needed to other studies — that regular physical exercise get them to a clinic.” says Kuh. All rights reserved 3 M A RC H 2 0 1 1 | VO L 4 7 1 | NAT U R E | 2 3 COURTESY OF P. but by this stage the nurses an epidemiologist who is leading the cognition were staggering under all the equipment. today — and they had maintained a healthy “You wobble rather more and I ended up hopweight throughout young adulthood. and that he can no longer fat as children — a sharp contrast to those of stand on one leg for long with his eyes closed. Hardly any of the Douglas exam. “so far without success”. here is very clear-cut evidence ber to visit one of a number of clinics around of something you can do to protect your cognithe country and had established a dedicated tive health as you get older. cohort ages and falls ill. but you say. if it did. the project’s future was again in jeopardy. this is science. and Ward has kept himself trim. variants later than those who had performed poorly4. who Yet Kuh and others emphasize that fates are not fixed by early life. “I should lead it. high IQ scores could indicate a brain that of obesity-linked genes.” she says. cian with the survey. Hardy the association. points to evidence from really understand the participants’ physiology the 1946 cohort — and supported by many and biology. are these life effects we see in mid life going to wane?” says Kuh. including whelmed by that onslaught of fat-promoting influences in the 1980s. “We didn’t know if the study would be closed down — don’t ever want the findings to be interpreted as purely determinisand Mike was retiring. geneticists and other scientists who want was 15 stone. MALVERN . When she destruction every social and behavioural pathway. eating out was more he had to prepare as a “serious challenge”.” says Richards. The MRC was pondering whether to keep paying for it and. Kuh says that she has been testing whether genes are responsible. that of some areas that respond to hormones or are responsible for hora possibility that might become clearer when she tests a further panel mone production.” says Richards. and aged 51. then weakened as the cohort grew older. all the education.” He recalls the food diary incomes were climbing. To studies on the group. race in central London. But once the researchers considered adult life. get more dramatic with age? Kuh is also thinking about how best to exploit genomic and other biomedical analyses. “You affordable. plotting the proportion who were obese edged hang on. Until that time. The 1980s brought a vivid lesson in the power Ward went to a clinic in Manchester for his of environment. I’ve got to tell the truth”.” says Kuh. Perhaps. and cars were the way to get around. But now ping about the place. tic. upwards. diet or other factors can shift poor examinations had been performed at the study trajectories to better ones. we threw almost analysed DNA collected from the cohort in 1999. It was a very unstable period. a statistihad performed well on childhood intelligence holding one of her grandchildren. By 2008 she had convinced cognitive decline with age. It was the pâté and the baguettes to collaborate to lengthen. lic5. genetics. “We tested almost to of which have been identified as risk factors for obesity6. it began to make sense. In 2005. Their theory now is that childspeculates. “One big question we can ask is. was well-developed all round. a of the cohort’s life-course data combined with more mysterious pattern emerged: those who Patricia Malvern aged 16. In short. the study will continue by living in the Peak District. and that medical data that Wadsworth had been collecting. “People appreciate a free in a person’s thirties and forties can slow their bone scan. Or will they. And Kuh and her colleagues — the study now although those in lower socioeconomic brackets has about 25 full-time researchers and support did get fatter faster. nourished on post-war rations. Rebecca Hardy.

et al. “The questions are. For now. et al. 1970 and 2000.000 children from before birth to age 21. Hum. and she suspects that these women took advantage of the educational and health opportunities afforded by post-war Britain to improve themselves. she acknowledges. The falling cost of DNA sequencing means that ploughing through participants’ entire genomes is an almost inevitable step. I learned all about how to address the Queen. “and the response rates were over 90% probably because people didn’t think they could choose not to participate. “I wrote such a nice letter. “it helps you accept that you’re mortal.. Hardy. Wadsworth had considered and rejected the idea of a 50th.” he adds.P.” Some 13% of subjects have died so far — and the study already has something to say about the fate of the rest. “Just things like bed-wetting. D. “I feel a huge responsibility to deliver. illegitimate children were turfed out of the study. Margetts. can you come back with a hypothesis?” Even so. 6. now all transferred from punch cards to computers. she says. & Simmonds. In the early years of the study. you’re not going to last forever. & Colley. 2. Kuh has more immediate planning concerns: five 65th-birthday parties. 577–580 (1989). Barker. 291. separated by father’s social class. J. “I suppose.. the members receive a birthday card. Kuh flips open some graphs of survival rates that she has calculated.” he says. Cripps. (She even wrote to Buckingham Palace to request a garden-party invitation for the study members. 1565–1573 (2009). at which the study members will meet each other for the first time. R. Br. Winter. “You’re very aware that your memory is going. e1–9 (2011). In the United States. The girls.” says Ward. we thought people might leave their partners and get off with someone in the study. the 1946 British birth-cohort study has lessons to offer its younger siblings.” ■ SEE EDITORIAL P. H. 40. over the years I began to feel I knew the team members.”) Ward and Malvern are pleased to have been part of the study. 545–552 (2010).. Soc. P. J. which aims to follow some 100. R. 7. C. well.. & Power. What did I contribute to the nation’s store of knowledge on bed-wetting?” Neither is perturbed by the idea of the researchers watching them until they crumble and die.” she says. Every year. Wadsworth.or 60th-birthday bash. whether men and women. cell lines frozen in liquid nitrogen — and in their records. 19. whose death rate is about half that of everyone else7. Kuh. 5. J. “people are amazed”. Int.” says Ward. Kuh has not been able to attribute the effect to less smoking or other obvious factors. In 1946. if they got through. like every other enquiry from the participants. Diana Kuh. “They really changed their lives with education. J. British birth cohorts were started in 1958. 68. Kuh says that this relationship has been crucial to keeping an average of 80% of the original cohort in the study. One participant. Am.NEWS FEATURE she has. Epidemiol. All rights reserved . recruitment and consent issues were a lot simpler: “If someone was willing to see you. J.” says Kuh. 4.” says Ward. dedicated leaders and a relatively low budget. that was consent.. and I’m still hoping to get a reply. Med. Genet. born into comfort or poverty. DUNHAM/NATURE CARDS & CALLS How to keep a cohort together — for 65 years After tracking its subjects’ health and well-being for longer than any other study. PEARSON/M. “But you also know that in the archive is a version of you. The parties are causing her some anxiety. 1534–1538 (1985). director of the 1946 survey. M. 1. They show the proportion of the survey members surviving up to age 60. Epidemiol. et al. When leaders of other studies hear that figure. 475–482 (2005). 1008– 1015 (2008). I say.” Yet the study is lending a touch of immortality to all its participants. 2 4 | NAT U R E | VO L 4 7 1 | 3 M A RC H 2 0 1 1 © 2011 Macmillan Publishers Limited. they did really well. “Somehow. T. that sounds very interesting. R. Mol. and another is provisionally planned.” “I often call it an alternative biography in there. C. D. Yet other cohort studies have been felled by bureaucratic infighting. questions about money and sex were “off the table”. she knows that working out how to incorporate these technologies “is going to be key”. 3. Kuh. spiralling costs or a lack of sustained funding. in case the get-together ended up influencing the participants’ life course in some way. Kuh says that she views the latest molecular biology techniques with caution. “Basically. when Kuh compiles a plan for the MRC’s fiveyearly review of the survey in 2012. E. Menopause 12.. Traces of them will live on in preserved DNA. et al. D. although I had never met any. A. B. when is the best time — and what would we learn from it?” The research team never forgets to send birthday cards to the cohort. children are being enrolled in the National Children’s Study.” says Kuh. Kuh. D. D. But Kuh decided that recognizing and rewarding the members was worth the risk. 168. E. Sci. “and that I’d quite like to get my hands on. attributes its survival to having fairly autonomous. really.” H. Osmond. “It gives me a fair old bit of pride in a way. But some factors in its success can’t be duplicated today. Quite often. R. Kuh points out a blue line representing a group of women from better-off backgrounds.” Those simpler days also brought constraints. “We’ve always had to offer good value for money. Midwinter. D. Kuh. Kuh and her colleagues responded to those complaints. Lo Conte.” One year the card showed a sunset. Med.” The 1946 study also shows that building a strong relationship with the participants is vital. and mothers were not asked whether they smoked in pregnancy because “the minister for health was telling the soldiers to smoke. says that the card means a lot to her. she says. S.. H. And they reveal yet another curious correlation for Kuh and her colleagues to dig into. R. signed by the research team and telling them about the latest results. P. “But that’s part of being the history of science. and some recipients complained about the suggestion that they were entering the evening of life. Lancet 334. J. L. outside researchers have an attitude of “give us all the cohort data and we’ll rush this through and find millions of associations. Patricia Malvern.5 Helen Pearson is Nature’s chief features editor. Li.. J. with personal letters or calls. Hardy.